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Friday, October 12, 2007

INTRODUCTION — Prostate cancer screening involves testing for cancer in men who have no symptoms of the disease. This testing can find cancer at an early stage, when it may be more easily and effectively treated. However, medical experts disagree about whether prostate cancer screening is right for all men, and it is not clear if the benefits of screening outweigh the risks.

This topic review is designed to discuss the advantages and disadvantages of prostate cancer screening. Men should talk with their healthcare provider to decide what is best in their individual situation.

WHAT IS PROSTATE CANCER? — Prostate cancer is a malignancy of the prostate, a small gland in men that is located below the bladder and above the rectum (show figure 1). The prostate produces seminal fluid that helps carry sperm during ejaculation.

According to the American Cancer Society, about 234,000 men in the United States will be diagnosed with prostate cancer in 2006, and over 27,000 will die from this disease. Prostate cancer is the second most commonly diagnosed malignancy after skin cancer.

Although many men are diagnosed with prostate cancer, most of them do not die from their cancer. While the lifetime risk of being diagnosed with prostate cancer is about 17 percent, only 3 percent of men die from the disease. Furthermore, autopsies show that 30 percent of men 50 years and older die with undiagnosed prostate cancer. This suggests that prostate cancer may grow so slowly that many men die of other causes before they even develop symptoms of prostate cancer.

RISK FACTORS

Age — All men are at risk for prostate cancer, but the risk greatly increases with older age. Doctors rarely find prostate cancer in men younger than 50 years old.

Ethnic background — Black men develop prostate cancer more often than white men. They also are more likely to die of prostate cancer than white men.

Family medical history — Men who have a first-degree relative (a father or brother) with prostate cancer are more likely to develop the disease.

Diet — A diet high in animal fat may increase a man's risk of prostate cancer.

Digital rectal examination — The DRE is performed by a healthcare provider in the office by inserting a gloved, lubricated finger into the rectum to feel for any lumps or irregularities in the prostate gland (show figure 2). DRE can detect some cancers that are missed by the PSA test. However, because it is not possible to reach all areas of the prostate, some tumors can go undetected using this screening method alone. Additionally, microscopic prostate cancers are impossible to detect by touch, no matter where they are located.

Prostate specific antigen — PSA is a protein produced by the prostate. The serum PSA test measures the amount of PSA in a sample of blood. Although many men with prostate cancer have an elevated PSA concentration (greater than 4.0 ng/mL), a high level does not necessarily mean there is a cancer. The most common cause for an elevated PSA is benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate. Other benign causes include prostate infection (prostatitis) and trauma. Trauma may be caused by bicycle riding or sexual activity; thus, the PSA should not be measured for 48 hours after these activities.

Generally speaking, the higher the PSA, the greater the chance that a cancer is present. However, in some studies, over 20 percent of men with prostate cancer had a normal PSA (false-negative test), while up to 40 percent of men without cancer had an abnormal PSA (false-positive test). Overall, only 30 percent of men with abnormal values will have prostate cancer.

Thus, the PSA test is not 100 percent accurate. False-negative results can delay diagnosis until the cancer is more advanced and less likely to be curable. False-positive results, which are common, can cause anxiety and lead to further testing that is more expensive to perform and is uncomfortable for patients.

Refinements in PSA blood testing such as measuring PSA velocity (rate of change over time), PSA density (PSA per volume of prostate tissue), free (unbound) PSA, and complex (bound to protein) PSA are intended to increase the accuracy of PSA tests, but there is not general agreement about the additional benefits of these tests.

If the DRE or PSA test is positive — A positive DRE or PSA test is not a reason to panic; benign conditions are the most common causes for an abnormal test, particularly for PSA tests. On the other hand, a positive test should not be ignored. Other tests, like transrectal ultrasound and prostate biopsy, are needed to evaluate a positive DRE or PSA.

Transrectal ultrasound — Transrectal ultrasound can be done in an office, and no sedation or anesthesia is needed. A small probe, about the size of a finger, is inserted into the rectum, and uses sound waves that bounce off the prostate to create an echo. A computer translates these echoes into an image (called a sonogram) of the prostate. About 80 percent of cancers have an abnormal ultrasound image. Transrectal ultrasound can also help to guide a surgeon to biopsy any area that appears abnormal.

Prostate biopsy — Prostate biopsy is also performed without sedation or anesthesia. It is done by inserting a small device into the rectum that can take a small sample of any suspicious areas (found either with DRE or ultrasound). Tissue samples are also taken from the base, middle, and tip of each side of the prostate. Some men experience temporary, mild rectal bleeding or blood in the urine or semen after this procedure. Rarely, biopsy can cause heavy bleeding or infection.

Up to one in five men with a negative result on an initial biopsy may have cancer diagnosed after subsequent biopsies. In addition, prostate biopsy can detect clinically unimportant cancers that are unlikely to cause illness or death; subsequent treatment for these cancers can ultimately cause more harm than good.

Summary — No screening test for prostate cancer is perfect. Experts who favor it suggest that the best screening strategy combines DRE with PSA testing, followed by transrectal ultrasound-guided prostate biopsy if either test is positive.

PROS AND CONS OF SCREENING — There are a number of arguments for and against prostate cancer screening.

Arguments for screening — Experts in favor of prostate cancer screening cite the following arguments: Even though many men with prostate cancer have nonaggressive tumors and do not die of the disease, the cancer is so common that a substantial number of men die from the cancer every year and many more suffer from the complications of advanced disease. For men with an aggressive prostate cancer, the best chance for curing it is probably by finding it at an early stage through screening and then treating it with surgery or radiation. Studies have shown that men who have prostate cancer detected by PSA screening tend to have earlier-stage cancer than men who have a cancer detected by other means. (See "Patient information: Advanced prostate cancer" and see "Patient information: Treatment for early prostate cancer"). The five-year survival for men who have prostate cancer confined to the prostate gland (early stage) is nearly 100 percent; this drops to 30 percent for men whose cancer has spread to other areas of the body. Chemotherapy and radiation therapy are relatively ineffective once prostate cancer has spread outside the prostate gland. The available screening tests are not perfect, but they are fairly good compared with screening tests for some other cancers, and they are easy to perform. The death rate due to prostate cancer has declined in recent years. This may be due to increased screening or improvements in prostate cancer treatment, particularly for advanced cancers. The death rate may also have declined due to changes in the ways that physicians complete death certificates.

Arguments against screening — The main argument against screening is that it is not clear if screening and treatment help men live longer and/or avoid the complications of advanced prostate cancer. No well-performed studies have determined that prostate cancer screening in the general population saves lives. Studies are currently underway to answer this important question, but the results may not be available for some time.

Other arguments have also been made against screening: Because of the relatively high number of false-positive DRE and PSA tests, a number of screened men will undergo unnecessary further testing with transrectal ultrasound and prostate biopsy. These secondary tests are relatively safe to perform, but they are not totally without side effects, and they add further costs. The side effects of treatment for early prostate cancers that are detected with screening may be substantial. Surgery and radiation therapy are the most popular therapies, and both can cause erectile dysfunction, urinary incontinence, and bowel problems. Although there are some tools to predict which cancers are more aggressive than others, these tools are not always accurate.

Many prostate cancers detected with screening are unlikely to cause death or disability. Thus, a number of men will have to experience the side effects of surgery and radiation for cancers that would never have bothered them had they gone undetected. In other words, even if the screening process works and a cancer is detected, it is not clear in all cases that the treatment is more beneficial than harmful.

PREVENTION OF PROSTATE CANCER

Supplements — Studies suggest that vitamin E and selenium supplements may protect against prostate cancer, but there is not enough evidence to recommend these supplements to all men.

Medications — Finasteride (Proscar®) has been shown to reduce the risk of developing prostate cancer by about 25 percent. However, aggressive cancers were diagnosed more frequently during the first year in men treated with finasteride than in those taking a placebo (look-alike substitute that contains no medication) pill. The reasons for this finding are not clear. It is not clear if finasteride should be offered to men at high risk for prostate cancer.

RECOMMENDATIONS

Professional organizations — Major medical associations and societies have issued conflicting recommendations regarding screening, making it difficult for an individual to decide if screening is right. The United States Preventive Services Task Force [2] and many European cancer societies have not endorsed routine serum PSA screening for the early detection of prostate cancer, while the American Cancer Society [3] and American Urological Association [4] do recommend screening. With currently available data, it is not possible to determine if the benefits of screening outweigh the significant risks associated with treatment.

A number of studies are expected to be completed over the next several years that should help clarify this controversy. In the meantime, the American Cancer Society, American Urological Association, and American College of Physicians recommend that men have an open discussion with their clinician.

The best way to decide if prostate cancer screening is right is to: Consider individual prostate cancer risk factors Know the potential benefits and harms of screening, diagnosis, and treatment Talk to a clinician about concerns or questions.

For men who choose screening — If a man chooses to have screening, he should begin at age 50. Men with risk factors for prostate cancer (such as black men or a man with a father or brother who had prostate cancer) may want to begin screening at the age of 45.

Screening should continue yearly once it is started, though less frequent testing may be appropriate for some men with a low PSA. For men who choose screening, we suggest that those with a PSA level below 1.0 ng/mL consider having PSA testing every four years and that those with a higher PSA level consider having PSA testing annually. We suggest that men who choose screening have an annual digital rectal exam, regardless of their PSA level.

Screening not recommended — Screening should not be performed in men who are 75 years and older or who have serious health problems; these men are unlikely to live long enough to benefit from screening and/or treatment.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute

1-800-4-CANCER (www.cancer.gov/cancertopics/screening/prostate)People Living With Cancer: The official patient information

website of the American Society of Clinical Oncology (www.plwc.org/portal/site/PLWC)National Comprehensive Cancer Network